Biopharma Business

Brexit – the stark reality is that the UK’s EU membership and the application of all EU legislation in the UK ends automatically at midnight on 30th  March 2019! Current understanding is that a Withdrawal Agreement will be developed that will provide for withdrawal by the UK from various treaties and will outline the terms of the future relationship between the UK and the EU. This Agreement will need to be approved and ratified by the UK Houses of Parliament, the European Parliament and EU-27 and perhaps 11 regional assemblies. You can get a sense from this that it will not be achieved easily or quickly. The end of the UK’s membership of the EU will happen on 30 March 2019 regardless of the outcome of the negotiations on the Withdrawal Agreement.

It is interesting to note that the topics to be covered in the Withdrawal Agreement (e.g. status of rights of UK citizens; migration controls; common travel areas…) do not relate in any significant way to topics of direct and immediate interest to pharmaceutical businesses. Crucial issues to business will, in the main, be negotiated after the Withdrawal Agreement is approved.

Theresa May – Prime Minister  has confirmed the need to have a transitional arrangement “should” the UK leave the EU on March 2019. Use of the term “should” is interesting. We would suggest that it can only be interpreted as “when” at this point and that our sector must plan on the basis that the exit will happen on 30 March 2019.

The UK’s stated intention is to maintain alignment with the EU. It has tabled a number of position papers (c.14) but we understand that these are light on specifics of what the proposals are to enable the transition. The negotiations between the EU and the UK do not appear to have progressed to a point where there is any clear understanding of what the provisions of the withdrawal will be. In this context, it must be questioned if a 2-year transitional arrangement is realistic. It is not possible for businesses to anticipate at this point what the provisions of the transition are likely to be.

The upshot is that pharmaceutical businesses need to plan for the worst case i.e. that the UK will be outside the EU at midnight on 30 March 2019. An MRA between the UK and EU/EEA makes sense to minimise the impacts for the sector; however, in our view, it is unlikely that this will be in place by the exit date.

Key areas for consideration by the pharmaceutical industry are as follows:

1. Relocation of the EMA from London to an EU Member State – This is a reality and there is a very competitive bid in progress by a number of Members States to house the agency. The decision of the EU Commission on the new location of the EMA is due to be announced in November 2017. The relocation will have a number of impacts, primarily related to changes to product registrations held with the EMA.
2. MA Holder – this will need to be an entity within the EU. MA’s held by a legal entity in the UK or authorised centrally through the EMA will need to be transferred to a legal entity in the EU. Regulatory agencies (e.g. HPRA) are focusing on managing the continued availability of medicines in their Member States and are liaising with the industry in this regard. The time required to achieve the transfers demands action by the industry as a matter of priority.
3. Brexit will introduce a need for a separate registration process in the UK for a company to access the UK market with its products. What will the UK registration process look like? This is an unknown currently, particularly in light of the workload that will attach to it for the MHRA and the implications for it to be able to handle applications within timeframes that meet business needs of the industry.
4. Market exclusivity for orphan drugs – the 10 year exclusivity period and the 6-month supplementary protection certificates are part of EU legislation. What will apply to products marketed in the UK once the UK exits the EU? If the UK doesn’t mirror EU legislation, these rights will fall.  We understand that the UK Government has announced a Great Repeal Act that is expected to enact a lot of EU law into domestic law upon Brexit. This will be important for the immediate continuity of rights that are important to the pharmaceutical and medical device sectors.
5. Safety monitoring and the QPPV
   1. The QPPV needs to be located within the EU. If located currently in the UK, this will need to be transferred to an EU Member State.
   2. If safety monitoring activities and safety databases are located in the UK, it is likely that they can continue to be so after Brexit. However, there will be a requirement for companies to demonstrate oversight of the activities that will effectively be delivered from a 3^rd country. Quality Agreements may need to be updated to reflect the changed situation.
6. Batch Release – will need to be done within the EU for EU markets under an MIA that is held by a legal entity within the EU. If this is done under an MIA in the UK currently, it will need to be transitioned to an MIA holder in the EU.
7. As the UK will be a 3^rd country (i.e. outside the EU/EEA), importation of product manufactured in the UK will be considered importation into the EU and will need to be covered under an MIA. Retesting of commercial product on importation will be required if an MRA is not in place when the UK exits the EU. Batch release by an EU based QP will be required.
8. Exempt medicines- the UK is a source of these unlicensed medicines currently. With Brexit, an MIA will be required to import an exempt medicine into an EU Member State. We understand that importation testing may not be required. However, this will need to be clarified.
9. Supply Chain- the holder of a WDA (Wholesale Distribution Authorisation) will need to be located in the EU. Pharmaceutical companies may need to restructure their supply chains to ensure appropriately licensed partners are in place in the EU.
10. Dual product labelling for the UK and Ireland- it is unclear if this will continue to be acceptable post Brexit. It is likely that regulatory agencies will seek pragmatic solutions to minimise the impacts for the industry. These need to be considered on a case-by-case basis and require action by the industry as a matter of priority.
11. Clinical trials
    • Currently trial approvals are handled at a national level. However, under the new Clinical Trials Regulation, an application will be made through a single portal for all EU countries. The UK will be excluded from this, so companies will have to get a separate approval for a clinical trial in the UK.
    • Trial sponsors will need to be located within the EU. This will require transition where sponsors are located in the UK currently.

Will there be implications for trials in progress at the time of the UK’s exit? This is unknown currently. A transitional arrangement will need to be reached by 30 March 2019.

12.    Medical Devices

• Companies using Notified Bodies in the UK will need to transfer to Bodies located within the EU. The time required to achieve the transfers demands action by the industry as a matter of priority.
• Authorised Representatives (ARs) need to be located in the EU, so management of changes will be required by the industry. Labelling changes will be required associated with a change in AR. The time required to implement the changes demands action by the industry as a matter of priority. Phased changes may be achievable through negotiation with the national regulatory bodies

13.   IP – A Unitary Patent System is due to be introduced for EU Member States in 2018. Assuming the UK joins, Brexit may change the position of the UK. This will require  consideration as part of the UK’s exit agreement to avoid barriers to continuity of IP arrangements

14. Other considerations include product pricing impacts; parallel trade considerations; customs & tariffs impacts relating to the movement of materials….and probably lots more as yet unidentified or unexplored!

Amid the uncertainty one thing is sure – there will be change and as we all know, change needs careful management to protect against unintended consequences, particularly in the provision of medicines to the public.

McGee Pharma International founded by Ann McGee, former regulator with the IMB (now the HPRA in Ireland) now a Pharmalex company, offers a suite of services that supports a pharmaceutical company to set up its operations in the EU/EEA.

Pharmalex offers a suite of Regulatory Affairs and Pharmacovigilance services that can support your Brexit related transition activities.

Our team can support your organisation to ensure that your company is  ‘BREXIT-ready’.  Please contact us at +353 1 846 47 42 or info@mcgeepharma.com.